Mitochondria as targets for chemotherapy

被引:116
作者
Gogvadze, Vladimir [1 ]
Orrenius, Sten [1 ]
Zhivotovsky, Boris [1 ]
机构
[1] Karolinska Inst, Inst Environm Med, Div Toxicol, S-17177 Stockholm, Sweden
基金
瑞典研究理事会;
关键词
Mitochondria; Disease; Oxidative stress; Neurodegeneration; Cancer; CYTOCHROME-C RELEASE; PERMEABILITY TRANSITION PORE; MOTOR-NEURON DEGENERATION; PROGRAMMED CELL-DEATH; COENZYME Q(10); CYCLOPHILIN-D; SUPEROXIDE-DISMUTASE; OXIDATIVE STRESS; DRUG-RESISTANCE; CANCER-CELLS;
D O I
10.1007/s10495-009-0323-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mitochondrial malfunctioning is implicated in the pathogenesis of a variety of disorders, including cancer and multiple neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and Huntington's disease. Disturbance of mitochondrial vital functions, e.g., production of ATP, calcium buffering capacity, and generation of reactive oxygen species, can be potentially involved in disease pathogenesis. Neurological disorders caused by mitochondrial deterioration are often associated with cell loss within specific brain regions. In contrast, mitochondrial alterations in tumor cells and the "Warburg effect" might lead to cell survival and resistance of tumor cells to chemotherapy. This review is devoted to the role of mitochondria in neurodegeneration and tumor formation, and describes how targeting of mitochondria can be beneficial in the therapy of these diseases, which affect a large human population.
引用
收藏
页码:624 / 640
页数:17
相关论文
共 128 条
[21]   Mitochondria dysfunction of Alzheimer's disease cybrids enhances Aβ toxicity [J].
Cardoso, SM ;
Santana, I ;
Swerdlow, RH ;
Oliveira, CR .
JOURNAL OF NEUROCHEMISTRY, 2004, 89 (06) :1417-1426
[22]   The parkinsonian neurotoxin MPP+ opens the mitochondrial permeability transition pore and releases cytochrome c in isolated mitochondria via an oxidative mechanism [J].
Cassarino, DS ;
Parks, JK ;
Parker, WD ;
Bennett, JP .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 1999, 1453 (01) :49-62
[23]   Mitochondrial dysfunction in S0D1G93A-bearing astrocytes promotes motor neuron degeneration:: Prevention by mitochondrial-targeted antioxidants [J].
Cassina, Patricia ;
Cassina, Adriana ;
Pehar, Mariana ;
Castellanos, Raquel ;
Gandelman, Mandi ;
de Leon, Andres ;
Robinson, Kristine M. ;
Mason, Ronald P. ;
Beckman, Joseph S. ;
Barbeito, Luis ;
Radi, Rafael .
JOURNAL OF NEUROSCIENCE, 2008, 28 (16) :4115-4122
[24]   Edaravone protects against MPP+-induced cytotoxicity in rat primary cultured astrocytes via inhibition of mitochondrial apoptotic pathway [J].
Chen, Hui ;
Wang, Sen ;
Ding, Jian-Hua ;
Hu, Gang .
JOURNAL OF NEUROCHEMISTRY, 2008, 106 (06) :2345-2352
[25]   Anglostatin-like activity of a monoclonal antibody to the catalytic subunit of F1F0 ATP synthase [J].
Chi, Sulene L. ;
Wahl, Miriam L. ;
Mowery, Yvonne M. ;
Shan, Siqing ;
Mukhopadhyay, Somnath ;
Hilderbrand, Susana C. ;
Kenan, Daniel J. ;
Lipes, Barbara D. ;
Johnson, Carrie E. ;
Marusich, Michael F. ;
Capaldi, Roderick A. ;
Dewhirst, Mark W. ;
Pizzo, Salvatore V. .
CANCER RESEARCH, 2007, 67 (10) :4716-4724
[26]   Huntingtin-interacting protein 1-mediated neuronal cell death occurs through intrinsic apoptotic pathways and mitochondrial alterations [J].
Choi, Shin Ae ;
Kim, Steven J. ;
Chung, Kwang Chul .
FEBS LETTERS, 2006, 580 (22) :5275-5282
[27]   Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin [J].
Clark, Ira E. ;
Dodson, Mark W. ;
Jiang, Changan ;
Cao, Joseph H. ;
Huh, Jun R. ;
Seol, Jae Hong ;
Yoo, Soon Ji ;
Hay, Bruce A. ;
Guo, Ming .
NATURE, 2006, 441 (7097) :1162-1166
[28]   Therapeutic effects of coenzyme Q10 (CoQ10) and reduced CoQ10 in the MPTP model of Parkinsonism [J].
Cleren, Carine ;
Yang, Lichuan ;
Lorenzo, Beverly ;
Calingasan, Noel Y. ;
Schomer, Andrew ;
Sireci, Anthony ;
Wille, Elizabeth J. ;
Beal, M. Flint .
JOURNAL OF NEUROCHEMISTRY, 2008, 104 (06) :1613-1621
[29]   The Bcl-2 family: roles in cell survival and oncogenesis [J].
Cory, S ;
Huang, DCS ;
Adams, JM .
ONCOGENE, 2003, 22 (53) :8590-8607
[30]   The mitochondrial permeability transition pore and its role in cell death [J].
Crompton, M .
BIOCHEMICAL JOURNAL, 1999, 341 :233-249